反应详情

To a suspension of 77.9 g (524.1 mmol) of 2H-azepin-7-amine, 3,4,5,6-tetrahydro, monohydrochloride (synthesis as described in WO96/14844 or Journal of Medicinal Chemistry (1998), 41(9), 1361-1366 or by analogy with the method described in example 1, step 1.1. and 1.2 using ε-caprolactam instead of (+/−)-3-phthalimidopiperidin-2-one) in 390 mL of ethanol was added 72.4 g (524.1 mmol) of potassium carbonate. The reaction mixture was stirred at room temperature for 10 min, 101.7 g (524.1 mmol) of ethyl 3-(4-pyrimidinyl)-3-oxopropionate was added and the resulting mixture was stirred under reflux for 16 h. The cooled solution was evaporated to remove solvent. The mixture was dissolved in dichloromethane, washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was filtrate through a pad of silica, rinsing with dichloromethane and then ethyl acetate. After evaporation, the resulting solid was triturated with diethyl ether to afford 36.4 g (28%) of pure product as a white-brown powder.

1. customsynthesis
2. stirringthe resulting mixture was stirred
3. temperatureunder reflux for 16 h
4. customThe cooled solution was evaporated
5. customto remove solvent
6. dissolutionThe mixture was dissolved in dichloromethane
7. washwashed with a saturated aqueous solution of sodium chloride
8. dry with materialdried over sodium sulfate
9. customevaporated to dryness
10. washrinsing with dichloromethane
11. customAfter evaporation
12. customthe resulting solid was triturated with diethyl ether